Should preclinical studies be registered?

Abstract

In recent years, numerous journals, regulators and ethics guidelines have adopted policies for prospective registration of clinical trials and full reporting of results. Whereas at one time, investigators published controlled clinical trials at their discretion, policies now compel prospective registration and deposition of trial results-including those that are negative and inconclusive-in publicly accessible databases 1 . In May, an editorial in Nature Biotechnology also supported the full disclosure of trial results in response to a call for more openness from European regulators 2 . In the following correspondence, we examine whether arguments that justify trial registration also hold for preclinical studies aimed at supporting trials. We argue that the high rate of failure in translating basic research into medical therapies raises concerns about human protections and inefficiencies in the research enterprise; registration and reporting of preclinical studies would partly address these concerns. We close by suggesting that funding agencies and others establish working groups to explore mechanisms for reconciling preclinical registration with the strategic imperatives in drug development.When registration and public deposition of results ('good disclosure practice') were canonized as ethical principles, two main arguments were offered. First, good disclosure practice respects the altruism of human subjects by helping ensure that studies see the light of day. Publication is the first step in a process through which findings in isolated settings are synthesized into collective knowledge. If this process is interrupted by nonpublication, burdens endured by human volunteers lose their moral justification. The second argument rested on protecting downstream users-patients and institutions whose interests are bound up with an unimpeded flow of findings. Absent good disclosure practice, researchers coming forward with unfavorable findings are at a reputational and funding disadvantage relative to those withholding them. This incentivizes biased reporting. Biased reporting potentially

Transparency of outcome reporting and trial registration of randomized controlled trials in top psychosomatic and behavioral health journals: A 5-year follow-up

“…Irreproducible studies are a major source of waste in research [31], and the need to improve transparency and reporting in preclinical studies cannot be overemphasized. In fact, the registration of confirmatory preclinical research has previously been put forward as one method of addressing this problem [37][38][39]. Thus, whether trials of interventions intended to improve health, which are published in top behavioral health journals, are construed as clinical or preclinical trials, it is imperative that they be registered.…”

Is animal research sufficiently evidence based to be a cornerstone of biomedical research?

“…[15][16][17][18][19] Several studies have shown that even the most promising findings from animal research often fail in human trials and are rarely adopted into clinical practice. [20][21][22] For example, one study found that fewer than 10% of highly promising basic science discoveries enter routine clinical use within 20 years.…”

“…13 In addition to intensifying the systematic review effort, providing training in experimental design and adhering to higher standards of research conduct and reporting, prospective registration of preclinical studies, 54 and the public deposition of (both positive and negative) findings would be steps in the right direction. 18 Greater public accountability might be provided by including lay people in some of the processes of preclinical research such as ethical review bodies 55 and setting research priorities. 28 However, if animal researchers continue to fail to conduct rigorous studies and synthesise and report them accurately, and if research conducted on animals continues to be unable to reasonably predict what can be expected in humans, the public's continuing endorsement and funding of preclinical animal research seems misplaced.…”

Found in Translation

“…Use meta-analysis of preclinical studies 134 Establish international multicenter phase III preclinical trials 135 Establish registries of preclinical studies 122,136 by guest on May 11, 2018 http://stroke.ahajournals.org/ Downloaded from…”